Early transient suppression of immune checkpoint proteins T-cell immunoglobulin mucin-3 and programmed cell death-1 in peripheral blood lymphocytes after blastocyst transfer is associated with successful implantation

ZHANG, Tao, ZHU, Wenyue, ZHAO, Yiwei, CHEUNG, Wing Ching, LIU, Yingyu, CHEN, Xiaoyan, DU, Yan, LEUNG, Kam Tong, CHAN, Yiu Leung, WANG, Chi Chiu, LAIRD, Susan and LI, Tin Chiu (2020). Early transient suppression of immune checkpoint proteins T-cell immunoglobulin mucin-3 and programmed cell death-1 in peripheral blood lymphocytes after blastocyst transfer is associated with successful implantation. Fertility and Sterility, 114 (2), 426-435.

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Abstract

Objective To compare the changing peripheral levels of immune checkpoint proteins T-cell immunoglobulin mucin-3 (Tim-3)/galectin-9 (Gal-9), and programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) over a 9-day period after blastocyst transfer between women who did and did not conceive. Design Prospective observational study. Setting University teaching hospital. Patients(s) Fifty-one infertile women undergoing day-5 blastocyst transfer. Intervention(s) Serial blood samples obtained on the day of embryo transfer (ET), and 3, 6, and 9 days afterward for measurement of membranous Tim-3 and PD-1 expression on various peripheral lymphocytes by flow cytometry, and serum concentrations of ligands Gal-9 and PD-L1 by ELISA. Main Outcome Measure(s) Membranous Tim-3 and PD-1 expression on lymphocytes and serum Gal-9 and PD-L1 concentrations and comparison of results between pregnant and nonpregnant women. Result(s) In women who conceived, the measurements exhibited three different types of response: [1] a transient and statistically significant reduction of Tim-3+NK-like T cells, Tim-3+/PD-1+CD8+ T cells, and Tim-3+/PD-1+CD4+ T cells that returned back to baseline level 9 days after ET; [2] a reduction followed by steady increase to above baseline level on day 9 (Tim-3+CD56dimNK cells); [3] a steady increase in expression after ET to reach a level statistically significantly higher than that of the baseline by day 9 (Tim-3+CD56brightNK cells). Women who did not conceive showed no statistically significant fluctuation in any of the parameters measured across the four time pointswith exception of increased Tim-3 expression on NK cells on day 9. Conclusion(s) Successful blastocyst implantation is associated with a reduction of Tim-3 and PD-1 expression in peripheral lymphocytes on days 3 and 6 that is no longer apparent on day 9.

Item Type:	Article
Additional Information:	** Article version: AM ** Embargo end date: 31-12-9999 ** From Elsevier via Jisc Publications Router ** Licence for AM version of this article: This article is under embargo with an end date yet to be finalised. **Journal IDs: issn 00150282 **History: issue date 18-03-2020; accepted 11-12-2019
Identification Number:	https://doi.org/10.1016/j.fertnstert.2019.12.022
Page Range:	426-435
SWORD Depositor:	Colin Knott
Depositing User:	Colin Knott
Date Deposited:	23 Mar 2020 15:11
Last Modified:	18 Mar 2021 01:18
URI:	https://shura.shu.ac.uk/id/eprint/26006

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